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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 307 records · Page 17Linked to original sources
PubMed1996

The interaction of PTH and dietary phosphorus and calcium on serum calcitriol levels in the rat with experimental renal failure.

BACKGROUND: Renal failure results in decreased calcitriol production, a key factor in the development of secondary hyperparathyroidism. Phosphorus accumulation and high parathyroid hormone (PTH) levels, both inherent to renal failure, have different effects on calcitriol production; moreover, dietary calcium loading may have a separate inhibitory effect on calcitriol production. This study was designed to evaluate the relative effects of PTH and dietary phosphorus and calcium on serum calcitriol levels. METHODS: Renal failure was surgically induced and rats were divided into normal, moderate renal failure, and advanced renal failure based on the serum creatinine. Each group was subdivided and received either a high-phosphorus diet (HPD, 0.6% Ca, 1.2% P) or high-calcium diet (HCaD, 1.2% Ca, 0.6% P) for 14-16 days to determine the relative effects of dietary calcium and phosphorus loading on serum calcitriol. In addition the effect of PTH and phosphorus on calcitriol stimulation was determined with a 48-h PTH infusion combined with either a low (0.16%) or high (1%) phosphorus diet; both diets had negligible calcium (< 0.05%). RESULTS: With decreasing renal function, PTH increased and was greater in rats fed the HPD than the HCaD; serum calcitriol decreased as renal function decreased and was lower in normal rats and rats with moderate renal failure fed a HCaD (P < 0.01). The calcitriol response to a PTH infusion decreased as renal function decreased (P < 0.05) but was greater on a low- (0.16%) than a high- (1%) phosphorus diet (P < 0.05). CONCLUSIONS: Dietary calcium loading either directly decreases serum calcitriol or acts by modifying the stimulatory effect of PTH; the stimulatory effect of PTH on serum calcitriol is modified by dietary phosphorus; in moderate renal failure, serum calcitriol levels depend on a complex interaction between PTH and dietary calcium and phosphorus; and in advanced renal failure, serum calcitriol levels are low and are difficult to stimulate, presumably because of the loss of renal mass.

Animals↗
PubMed1995

Oligodendrocyte-reactive O1, O4, and HNK-1 monoclonal antibodies are encoded by germline immunoglobulin genes.

Natural or physiologic autoantibodies are present normally in serum, are polyreactive, are frequently of the IgM subtype, and are encoded by unmutated germline genes. We tested whether the oligodendrocyte-reactive O1, O4, A2B5, and HNK-1 IgM kappa monoclonal antibodies are natural autoantibodies by sequencing immunoglobulin (Ig) cDNAs and comparing these with published germline sequences. O1 VH was identical with unrearranged VH segment transcript A1 and A4. O4 VH had three and HNK-1 VH had six nucleotide differences from germline VH101 in the VH coding region. The D segment of O1 was derived from germline SP2 gene family. The D segments of O4 and HNK-1 were derived from DFL16 gene family. O4 JH and HNK-1 JH were encoded by unmutated germline JH4, whereas O1 JH was encoded by germline JH1 with one silent nucleotide change. O1 and O4 light chains were identical with myeloma MOPC21 except for one silent nucleotide change. HNK-1 V kappa was identical with germline V kappa 41 except for two silent nucleotide changes. O1 J kappa, O4 J kappa and HNK J kappa were encoded by unmutated germline J kappa 2. In contrast, A2B5 VH showed seven nucleotide differences from germline V1, whereas no germline sequence encoding A2B5 V kappa was identified. O1 and O4, but not A2B5 were polyreactive against multiple antigens by direct ELISA. Therefore, O1, O4 and HNK-1 Igs are encoded by germline genes, and have the genotype and phenotype of natural autoantibodies.

Amino Acid Sequence↗
PubMed1995

beta-Phenylethylamine regulation of dopaminergic nigrostriatal cell activity.

In the present paper, the action of beta-phenylethylamine on electrophysiological activity of dopaminergic nigrostriatal neurons is described. 10 s after its i.v. injection and during 2-4 min, beta-phenylethylamine decreased the firing rate, the number of spikes within and out of burst and the number of bursts per second of these neurons. This was a dose-related action with statistical differences starting from 1.4 mg/kg for total and out of burst firing rate and from 2.4 mg/kg for within burst firing rate and for the number of bursts per second. The standard deviation and the variation coefficient of inter-spike intervals increased in a dose-related way. The marked effect found after low-dose administration suggests that under physiological conditions endogenous beta-phenylethylamine levels regulate the nigrostriatal dopaminergic cell activity. After peripheral low dose administration, beta-phenylethylamine behaves as a dopaminergic agonist with a very fast and brief action.

Action Potentials↗
PubMed1995

VP1 and VP2 capsid proteins of Theiler's virus are targets of H-2D-restricted cytotoxic lymphocytes in the central nervous system of B10 mice.

Resistance to Theiler's virus-induced demyelination maps genetically to the MHC class I D region and is associated with up-regulation of class I products and the presence of MHC-restricted virus-specific cytotoxic CD8+ T cells in the CNS. To determine the targets of the cytotoxic response, transfected C57SV (Kb, Db) cells expressing LP (including the leader peptide, VP4, VP2, and VP3 coding sequences), VP4 (including the leader peptide and VP4), VP2, VP3, VP1, or RP (including P2 and P3) were generated. CNS-infiltrating lymphocytes obtained from virus-infected B10, B10.K (Kk, Dk), B10.RBF (Kb, Df). B10.RFB3 (Kf, Db), and B10.RBQ (Kb, Dq) mice were used as effectors. Specific cytotoxicity to the capsid proteins encoded in the LP construct, VP2 and VP1, was demonstrated to be H-2Db region restricted and was mediated by CD8+ T cells. No Kb-restricted virus-specific cytotoxicity response was observed. No specific cytotoxic response against RP-encoded proteins was observed in the CNS of B10 mice. Therefore, both VP1 and VP2 are targets for an H-2D-restricted cytotoxic immune response against Theiler's virus infection in the CNS of infected resistant B10 mice.

Animals↗
PubMed1995

Spontaneous and induced remyelination in multiple sclerosis and the Theiler's virus model of central nervous system demyelination.

Remyelination in the central nervous system, originally thought to occur rarely, if ever, is now an established phenomena in multiple sclerosis patients. However, the extent of myelin repair is incomplete and limited. Experimental models of central nervous system demyelination provide an opportunity to study the cellular and molecular events involved in remyelination. These models may provide some clue to why remyelination in multiple sclerosis is incomplete as well as suggest potential methods to stimulate central nervous system repair. In this review we examine the morphological aspects of central nervous system remyelination and discuss both spontaneous and induced remyelination in multiple sclerosis and experimental models of central nervous system demyelination. We give special emphasis to the Theiler's virus model of central nervous system demyelination and its usefulness to identify therapeutic agents to promote remyelination. The role of immunoglobulins in promoting remyelination in both the Theiler's model system and in multiple sclerosis is discussed. Finally, we examine the potential physiological role of demyelination and remyelination and its relationship with clinical manifestations of central nervous system disease.

Animals↗
PubMed1995

Experimental strategies to promote central nervous system remyelination in multiple sclerosis: insights gained from the Theiler's virus model system.

The destruction of central nervous system (CNS) myelin, the lipid-rich insulator surrounding axons in the mammalian brain and spinal cord, is the primary pathological finding in multiple sclerosis. Myelin loss can result in a significant clinical deficit, and was originally thought to be permanent, similar to axonal destruction. However, myelin regeneration is now an established phenomenon in both human disease and animal models of CNS demyelination. In this review, the concept of remyelination in demyelinating diseases such as multiple sclerosis is discussed and the usefulness of animal models of CNS demyelination in developing experimental strategies to promote remyelination is examined. Special emphasis is given to the Theiler's murine encephalomyelitis model, which has been the primary animal model used to investigate therapies designed specifically to stimulate myelin repair.

Animals↗
PubMed1995

A monoclonal autoantibody that promotes central nervous system remyelination in a model of multiple sclerosis is a natural autoantibody encoded by germline immunoglobulin genes.

Antibodies directed against self-Ags are frequently considered detrimental, and have been shown to play a pathogenic role in certain autoimmune diseases. However, the presence of autoreactive Abs in normal individuals suggests that some autoantibodies could participate in normal physiology. Our previous studies demonstrated that monoclonal autoantibodies SCH94.03 and SCH94.32, generated from the splenocytes of uninfected SJL/J mice injected with normal homogenized spinal cord, promote central nervous system remyelination when passively transferred into syngeneic mice chronically infected with Theiler's murine encephalomyelitis virus, an established experimental model of multiple sclerosis. In this study we show that these two monoclonal autoantibodies are identical, and have phenotypic characteristics of natural autoantibodies. By using a solid phase assay system, SCH94.03 and SCH94.32 showed reactivity toward several protein Ags and chemical haptens, with prominent reactivity toward spectrin, (4-hydroxy-3-nitrophenyl)acetyl, and fluorescein. Sequence analysis showed that both SCH94.03 and SCH94.32 were encoded by identical germline Ig light chain V kappa 10/J kappa 1 and heavy chain V23/DFL16.1/JH2 genes, with no definitive somatic mutations. These results indicate that a natural autoantibody participates in a beneficial physiologic response to central nervous system injury.

Amino Acid Sequence↗
PubMed1995

The independent gene amplification of electrophoretically indistinguishable B esterases from the insecticide-resistant mosquito Culex quinquefasciatus.

Resistance to organophosphates in Culex mosquitoes is typically associated with increased activity of non-specific esterases. The commonest phenotype involves two elevated esterases, A2 and B2, while some strains have elevation of esterase B1 alone. Overexpression of the two B esterase electromorphs is due to gene amplification. Full-length cDNAs coding for amplified esterase B genes from a resistant Cuban strain (MRES, with amplified B1 esterase) and a Sri Lankan strain (PelRR, with amplified B2 esterase) of C. quinquefasciatus have been sequenced. In addition, a partial-length cDNA coding for a B esterase from an insecticide-susceptible Sri Lankan strain (PelSS) has been sequenced. All the nucleotide sequences and the inferred amino acid sequences show a high level of identify (> 95% at the nucleotide and amino acid level), confirming that they are an allelic series. The two B1 esterase nucleotide sequences (MRES and the previously published TEM-R [Mouches, Pauplin, Agarwal, Lemieux, Herzog, Abadon, Beyssat-Arnaouty, Hyrien, De Saint Vincent, Georghiou and Pasteur (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 2574-2578]) showed the lowest identity, and restriction-fragment-length-polymorphism analysis of the two strains was different. On the basis of these data we suggest that the two electrophoretically identical B1 esterase isoenzymes from California and Cuba have been amplified independently. Alternatively, if amplification has occurred only once, the original amplification has not occurred recently.

Amino Acid Sequence↗
PubMed1995

Listeria monocytogenes: a live vector able to deliver heterologous protein within the cytosol and to drive a CD8 dependent T cell response.

After an introduction on the entry and lifestyle of Listeria monocytogenes within mammalian eucaryotic cells, this chapter gives a brief overview of murine experimental listeriosis. Among the main characteristics of this murine model of infectious/pathogenic processes initiated by a facultative intracellular bacteria, we point out two main recent advances. One relates to Listeria monocytogenes-induced production of cytokines as local, and transient signals able to direct the immune responses along a type 1 pathway of CD4/CD8 T cell differentiation. The other relates (a) to the recognition of L. monocytogenes-reactive CD8+ T lymphocytes as effectors able, once recruited within infected loci, to critically contribute to the complete clearance of the bacteria, and (b) to the recently recognized specificity of some of these CD8 lymphocytes in BALB/c mice. In this paper, we also briefly review (a) the readout assays presently used to monitor the outcome of the infectious/pathogenic processes and the related development and expression of immune responses induced by intravenous inoculation of wild-type virulent or attenuated L. Monocytogenes, (b) why all this information allows us to consider the use of L monocytogenes of attenuated virulence as relevant live recombinant vectors in order to deliver heterologous proteins to the class I processing and presentation pathway, and to induce CD8 T cells along the type 1 pathway.

Animals↗
PubMed1995

Paclitaxel: a radiation sensitizer of human cervical cancer cells.

Paclitaxel is an exciting chemotherapeutic agent active in a variety of malignant tumors. This study was designed to explore the radiosensitizing potential of paclitaxel in human cervical cancer cell lines. The cell lines ME180, SiHa, and MS751 were evaluated. Experiments were performed in the proliferative phase of growth. Paclitaxel doses were treated at 0.01x, 0.02x, 0.03x, 0.04x, and 0.05x peak plasma concentration (PPC) in ME180 and 0.001x, 0.002x, 0.003x, 0.004x, and 0.005x PPC in SiHa and MS751. Radiation (RT) doses of cobalt-60 were 0, 2, 4, 6, 8, and 10 Gy. In the combination group RT was given 48 hr after paclitaxel treatment. To allow for median effect analyses, combination doses were kept at a fixed ratio: 0.01x/2 Gy, 0.02x/4 Gy, 0.03x/6 Gy, 0.04x/8 Gy, and 0.05x/10 Gy for ME180 and 0.001x/2 Gy, 0.002x/4 Gy, 0.003x/6 Gy, 0.004x/8 Gy, and 0.005x/10 Gy in MS-751 and SiHa. Adenosine triphosphate bioluminescence was performed on Day 7 after treatment and compared to untreated controls. Dose-response data were fit to the linear quadratic model and mean inactivation dose D was calculated. Data analysis with t test was performed. The median effect principle was used to evaluate the nature of the interaction between the two therapeutic modalities. Paclitaxel increased radiation cytotoxicity in all three cell lines. Mean inactivation D values for RT versus combination were 6.70 (+/- 0.15) and 4.33 (+/- 0.43) (P = 0.004) in ME180, 6.08 (+/- 0.70) and 4.54 (+/- 0.093) (P = 0.033) in MS751, and 7.03 (+/- 0.46) and 5.97 (+/- 0.51) (P = 0.034) in SiHa. The interaction of paclitaxel and RT was found to be supraadditive in ME180 and SiHa and subadditive in MS751. We conclude that paclitaxel has modest radiation-sensitizing effects in cervical cancer cell lines and that further clinical trials should be considered.

Cell Survival↗
PubMed1995

Localization of foot and mouth disease virus RNA in tissue culture infected cells via in situ polymerase chain reaction.

Foot and mouth disease virus RNA was visualized in infected primary tissue culture cells by in situ PCR incorporating digoxigenin-labeled dUTP. The viral RNA polymerase gene was used as a target for amplification. Infected cells revealed cytoplasmic staining, predominantly perinuclear. The intensity of staining was in proportion to the degree of cytopathology observed and similar to the results obtained using immunoperoxidase staining. The in situ PCR technique for FMDV detection could be applied to formalin-fixed samples and be useful for the study of persistent infections.

Animals↗
PubMed1995

Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain.

The beta 3-adrenergic receptor (AR) is widely distributed in peripheral tissues, but up to now it has not been detected in the central nervous system. By using the polymerase chain reaction (PCR) technique, we found the beta 3-AR mRNA to be present in all the regions of the human brain we investigated. The quantities found were very low compared to those of the beta 1-AR and beta 2-AR mRNAs, being hardly detectable in adult brain. In contrast, the brain of very young infants contained about 100 times more beta 3-AR mRNA than the adult brain, whereas the amounts of beta 1-AR and beta 2-AR transcripts were essentially the same. In addition, using PCR we have cloned a central beta 3-AR coding region from a human frontal cortex cDNA library and have found it to be identical to the corresponding peripheral sequence.

Aged↗
PubMed1995

Idiopathic dialysis ascites in the nineties: resolution after renal transplantation.

The incidence of idiopathic dialysis ascites seems to have decreased since the introduction of more effective techniques for control of fluid overload and uremia in chronic hemodialysis patients. Most of the patients reported so far had some predisposing factor, such as malnutrition or sustained fluid overload. We report a case of idiopathic dialysis ascites in a young well-nourished woman with an excellent control of fluid overload and in whom biocompatible dialyzer membranes and volumetric controlled ultrafiltration had been used since her onset of chronic dialysis. Extensive studies excluded the existence of an underlying cause for ascites. Ascitic fluid had the characteristics of an exudate, and a peritoneal biopsy specimen showed chronic nonspecific inflammatory changes. Massive ascites persisted for 6 months, requiring repeated paracentesis, until the performance of a successful renal transplantation. Coinciding with the recovery of renal function, a dramatic disappearance of ascites was observed.

Adult↗
PubMed1995

Pharmacological evidence for the existence of different subtypes of muscarinic acetylcholine receptors for phosphoinositide hydrolysis in neonatal versus adult rat atria.

The negative inotropic effect of carbachol, as well as phosphoinositide hydrolysis, was measured in atria from neonatal and adult rats. Carbachol increased phosphoinositide hydrolysis and decreased dF/dt of both neonatal and adult atria; however, the neonatal atria showed hypereactivity to carbachol as compared with adult atria. Inhibition of phospholipase C reduced the supersensitivity to carbachol upon contractility in neonatal atria producing values similar to those of the adult atria, suggesting that muscarinic acetylcholine receptor (mAchR) stimulation is secondary to receptor-mediated hydrolysis of phosphoinositides. Pharmacological analysis with mAchR antagonists tends to support the idea that m1 and m2 subtypes are the most important mediators of the response to carbachol in neonatal atria. In adult atria, the effect of carbachol is coupled only to mAchR m2 subtypes.

Animals↗
PubMed1995

Disposal-related sharps injuries at a New York City Teaching Hospital.

OBJECTIVE: To characterize disposal-related sharps injuries. DESIGN: A three-part study including (a) descriptive analysis of disposal-related injuries in a 1-year period, (b) 4:1 matched case-control study of nurses injured while using sharps disposal containers, and (c) survey to solicit opinions of users of containers. SETTING: An 1,181-bed teaching hospital in New York City. PARTICIPANTS: For epidemiologic analyses, persons with self-reported injuries identified via New York State and Occupational Safety and Health Administration forms and control nurses without self-reported injuries. For survey, convenience sample of hospital nurses, laboratory workers, and maintenance workers. MAIN OUTCOME MEASURES: Circumstances of injuries determined by study questionnaires. Employee opinions obtained by questionnaires and discussions during small group sessions. RESULTS: Three hundred sixty-one persons reported sharps injuries, of whom 72 (20%) had disposal-related injuries. Persons with disposal-related injuries included four hospital visitors and one patient. Of 67 disposal-related injuries among employees, 25 (37%) directly involved use of a sharps disposal container. Significant risk factors for injury included container height greater than 4 ft above the floor, distance less than 5 ft from site of sharp object use to nearest container, and lack of attendance at universal precautions inservice classes. Survey groups involved 69 employees who identified a variety of preferred features for sharps disposal containers. CONCLUSIONS: Disposal of sharp objects is an important cause of sharps injuries. Ergonomic factors, worker education, and appropriate container design should be considered in injury prevention strategies. Relevant guidelines and regulations are lacking and are needed.

Case-Control Studies↗
PubMed1995

In vitro chemosensitivity of paclitaxel and other chemotherapeutic agents in malignant gestational trophoblastic neoplasms.

This is the first report on the ATP cell viability assay as a chemosensitivity test system for gestational trophoblastic neoplasms (GTN). We obtained chemosensitivity profiles in two established trophoblastic cell lines and four fresh tumors. Ten drugs were tested in vitro in the two cell lines JAR and JEG-3. The IC50 values of the 10 chemotherapeutic agents tested were very similar for both cell lines. The three most active drugs in these cell lines were VP-16, paclitaxel and vincristine. This is the first report on the activity of paclitaxel in trophoblastic cell lines. We furthermore evaluated this assay for chemosensitivity testing in four fresh malignant GTN tumors: one placental site trophoblastic tumor, one chorocarcinoma and two invasive moles. The placental site trophoblastic tumor specimen revealed to be rather chemoresistant in vitro whereas the other three tumors were chemosensitive. From our cell line data we conclude that the ATP cell viability assay is a practicable assay for chemosensitivity testing of GTN cell lines and gives repeatable results. However, the value of this assay for fresh GTN chemosensitivity testing needs to be defined.

Adenosine Triphosphate↗